Design, Synthesis, Molecular Docking, ADMET, and Biological Studies of Some Novel 1,2,3-Triazole Linked Tetrazoles as Anticancer Agents

Abstract

Background: 1,2,3–Triazolyl–tetrazoles have received substantial attention because of its unique bioisosteric properties and extraordinarily broad spectrum of biological activity, making them interesting for the drug design and synthesis of delightful class of widely investigated heterocyclic compounds. To address major health concerns, it is consequently important to devote ongoing effort for the identification and development of New Chemical Entities (NCEs) as possible anticancer medicines. Methods: We began our initial investigation of the reaction between 5-(azidomethyl)-1H-pyrrolo[2,3-b]pyridine, 1-phenylsubstituted-5-(prop-2-yn-1-ylthio)-1H-tetrazole under click chemistry to gave the corresponding triazole precursors and screened for their cytotoxicity reported by variations in therapeutic actions of parent molecule. All of the prepared scaffolds were characterised by proton, carbon resonance spectroscopy, IR, and mass spectral techniques. Results: When tested for in vitro antitumor activity that the prepared compounds 7e, 7h had a significant anticancer activity against human adenocarcinoma Hs766T cell line with IC50 = 5.33, 4.92 μg/mL and Hs460 cell line with IC50 = 4.82, 6.15 μg/mL respectively. Final scaffolds 7f, 7h, 7j acquiring highest potential drug binding scores ΔG = –10.42, –8.80, –9.37 Kcal/, with amino acids residues Ala A:11 (2.195 A˚), Asp A:119 (1.991 A˚), Thr A:58 (1.890 A˚), Lys A:16 (1.253 A˚), Asp A:38 (2.013 A˚), Lys A:117 (2.046 A˚) respectively and processing Lipinski’s rule of five as good oral bioavailability agents. Conclusion: The molecular framework for the synthesis of novel azaindole 1,2,3–triazole scaffolds coupled to tetrazole core was discovered in our study and evaluation of anticancer activity.